Akikazu Udagawa

DNA Methylation Changes During Cleft Palate Formation Induced by Retinoic Acid in Mice

Objectives: The aim of this study was to analyze epigenetic (specifically, DNA methylation) participation in the mechanisms of cleft palate only induced by maternal exposure to all-trans retinoic acid in mice. Design: Cleft palate only was induced in fetuses by maternal exposure to all-trans retinoic acid. Their secondary palates were excised for analysis. Cytosine extension assay and restriction landmark genomic scanning were performed to analyze DNA methylation status. The expression levels of the DNA methyltransferases were examined by real-time reverse transcriptase–polymerase chain reaction. Results: Using cytosine extension assay, on gestation day 14.5, the status of DNA methylation within CpG islands and in global DNA was decreased significantly in all-trans retinoic acid–treated groups compared with the controls (p < .01 and p < .05). In the controls, the status within CpG islands on gestation day 14.5 was significantly increased compared with gestation days 13.5 and 18.5 (p < .01). Using real-time reverse transcriptase–polymerase chain reaction, there was no significant change in the expression of DNA methyltransferases, except on gestation day 18.5. Using restriction landmark genomic scanning on gestation day 18.5, five spots (0.49%) in the controls and one spot (0.1%) in all-trans retinoic acid–treated groups were specifically detected. Conclusions: These results indicate that changes in DNA methylation may play an important role in the manifestation of cleft palate only caused by environmental factors such as maternal exposure to all-trans retinoic acid.

Primary repair in adult patients with untreated cleft lip-cleft palate.

Background: The authors have volunteered their services as plastic surgeons in several countries, such as Nepal and Cambodia. In these programs, the authors saw many adults with cleft lips or palates who could not have primary repair at the proper time. The purpose of this report is to discuss the primary repair of untreated cleft lips or palates in adult patients. Methods: Subjects were older than 17 years. In Nepal, primary repairs were performed in 129 adults with untreated clefts over the past 11 years. Unilateral cleft lips were repaired by rotation advancement with the small triangular flap method or the straight method with a small triangular flap. Bilateral clefts were repaired using a one-stage repair method. Cleft palates were repaired by a mucoperiosteal push-back or Furlow technique. Results: Differences between primary cleft repair for infants and for adults were as follows: (1) in adults, aggressive correction was possible, as maxillary growth was not a consideration; (2) correction of the anterior part of the nasal deformity was more difficult than in infants, as adults showed less elasticity and a more severe deformity of the nasal cartilages; (3) simultaneous palatoplasty should be chosen judiciously, as it is more invasive and results in higher morbidity; and (4) cheiloplasty under local anesthesia can reduce cost, time, and manpower. Conclusions: These observations should be useful for the local and foreign surgeons who treat clefts in developing regions.

A simple reconstruction for congenital unilateral lower lip palsy.

Background: Congenital unilateral lower lip palsy or congenital hypoplasia of the depressor anguli oris muscle, also known as asymmetric crying facies, characterized by deformity of the lower lip, lacks aggressive surgical intervention methods. Although several dynamic and static reconstruction methods have been reported, textbooks introduce only passive surgical intervention, of weakening the unaffected side through techniques such as selective marginal mandibular neurectomy which, however, tends to produce lack of emotive movement. Therefore, a new surgical intervention for the reconstructive treatment of asymmetric crying facies is presented. Methods: A bidirectional (horizontal and vertical) fascia was grafted to restore the aesthetic appearance of the asymmetric lower lip. The horizontal fascial strip achieves restoration of the center of the lower lip to its proper position, whereas the vertical fascial strip achieves aesthetic symmetry of the lower lip at mouth opening. Each end of the vertical strip is anchored to the lower lip and the mandibular bone, respectively, thereby allowing simultaneous movement of the mandible and lower lip. Results: The reconstruction of unilateral lower lip palsy has been successfully performed on seven patients, with ages ranging from 2 years 9 months to 11 years 1 month, since June of 1996. Conclusions: The aim of this procedure is not to achieve complete dynamic reanimation. However, with regard to its simplicity and minimal invasiveness and the satisfaction of the patients, it is considered to be a well-balanced surgical intervention.

Tessier number 7 cleft with oblique clefts of bilateral soft palates and rare symmetric structure of zygomatic arch

Craniofacial clefts are very rare congenital deformities. Tessiers numbering classification is a simple system universally accepted. Excluding cleft lip and palate, the transverse or lateral cleft (Tessier number 7) is the most common type of craniofacial cleft, manifesting macrostomia without skeletal abnormalities. We present a case of Tessier number 7 cleft with oblique clefting of the soft palate bilaterally and rare symmetric structures of the zygomatic arch.

Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice

Background  Fat tissue is a common material for autologous transplantation in plastic and reconstructive surgery. Basic fibroblast growth factor (bFGF) ameliorates the fat graft survival. A transplantation model has shown the gene expression of matrix metalloproteinases (MMPs) to increase in adipocytes. The aim of this study is to investigate the role of MMPs in the amelioration of survival by bFGF.

Low-dose GH supplementation reduces the TLR2 and TNF-α expressions in visceral fat

The increased population of TLR2/TNF-alpha co-expressing adipocytes is associated with the development of insulin resistance. We have herein shown the significance of low-dose growth hormone (GH) supplementation for the regulation of TLR2 and TNF-alpha expressions in visceral fat using different kinds of mouse models fed with a high-fat diet. Low-dose GH supplementation reduced the increased population of TLR2/TNF-alpha co-expressing adipocytes in high-fat fed mice. The neutralization of IGF-1 abolished the effect of GH supplementation on the TLR2 expression using GH-overexpressing mice. IGF-1, but not GH, inhibited the FFA-induced TLR2 and TNF-alpha expression in 3T3-L1 cells. Finally, low-dose GH supplementation reduced the TLR2 expression without an obvious change in the visceral fat volume in ob/ob mice. These results indicate that low-dose GH supplementation possibly inhibits the high-fat induced change of the adipocytes to TLR2/TNF-alpha co-expressing cells through the action of IGF-1.

A case of accessory scrotum with perineal lipoma.

A 5-year-old boy was followed up with migratory spermatic cord and a perineal tumour at the paediatric department after birth. He was born by Caesarean section at 38 weeks in viviparity. Weight at birth was 3650 g. Although a meningocele in the sacral region was found by MRI, there were no symptoms in particular and no other deformity was found. When he was 4 years old, he presented to our department with the perinal tumour. On examination, a slender scrotum-like tumour covering the centre of the perineal lesion, along with inflammation and ulceration around the skin of the anus, was observed. Both testes and scrotums were observed in front of the tumour (Figure 1a). An excision of the tumour and Z-plasty of the perineal lesion were performed. The subcutaneous tissue consisted of adipose tissue-like lipoma and was resected along with the tumour (Figure 1b). A Z-plasty was carefully performed in order to maintain the lefteright symmetry of the

The "stepped caudal exposure" technique for excision of nasal dermoids with intracranial extension.

AbstractNasal dermoid sinus cysts (NDSCs) are rare congenital malformations derived from ectodermal and mesodermal tissues. There are numerous reports on surgical approaches for extirpation of NDSCs with intracranial extension. Here we describe the “stepped caudal exposure” approach, a technique that minimizes the risk for bacterial infection of the central nervous system from the nasal space. This procedure involves a stepwise osteotomy of the frontal and nasal bones that permits sufficient exposure to allow complete extirpation of NDSCs; it was used successfully to treat a 20-month-old boy with NDSC extending into the intracranial space and an infectious abscess. After NDSC extirpation and debridement of the abscess, the anterior skull base was reconstructed with bone grafts placed on both the intracranial and intranasal sides of the widened foramen cecum. Thereafter, each graft was covered by frontal pericranial flaps for blood supply. These modified surgical techniques may enhance the safety of surgical removal of NDSC, particularly in cases accompanied by infectious lesions such as abscesses.

Treatment of Velopharyngeal Inadequacy in a Patient With Submucous Cleft Palate and Myasthenia Gravis

Objective: To describe the clinical course and management of a patient with submucous cleft palate who developed myasthenia gravis (MG) as an adult and suffered recurrent hypernasality. Few reports have described MG patients undergoing pharyngeal flap surgery for velopharyngeal incompetence, and these have described only slight speech improvement in such patients. Design: Case report. Patient: The patient underwent primary pushback palatoplasty and superiorly based pharyngeal flap surgery for submucous cleft and short palate at age 7. Hypernasality showed major improvement after initial surgery. At age 19, the patient developed MG that triggered the recurrence of velopharyngeal incompetence. Intervention: After MG was treated, revision pushback palatoplasty was performed for velopharyngeal incompetence when the patient was 24 years old. Preoperatively and postoperatively, the patient was evaluated by the same speech-language-hearing therapists, each with at least 5 years of clinical experience in cleft palate speech. Results: After the second pushback palatoplasty, hypernasality and audible nasal air emission during speech decreased to mild. Conclusion: Primary pushback palatoplasty and pharyngeal flap surgery were performed for the submucous cleft palate. Revision pushback palatoplasty improved velopharyngeal inadequacy induced by MG. Decreased perceived nasality positively influenced the patients quality of life. Combined pushback palatoplasty and pharyngeal flap surgery is thus an option in surgical treatment for velopharyngeal inadequacy to close the cleft and the velopharyngeal orifice in cases of cleft palate and MG.

Hemi aplasia of the nose with complete cleft lip and palate of the contralateral side

Nasal aplasia, including hemi aplasia of the nose, is a rare congenital anomaly of the nose. Since the ipsilateral side tends to be affected more frequently than the contralateral side of the face in half nose anomalies, only reports concerning the ipsilateral defect are numerous. This report presents an unusual case of hemi aplasia of the nose with complete cleft lip and palate of the contralateral side. A local flap on the nasal dorsum was used for nasal reconstruction, where correction of the elongation of the inner canthal distance and the shape of the inner canthus was performed.